Cocaine is a commonly abused euphoriant with strong reinforcing effects. Animal data have shown, that the reinforcing properties are related to cocaine's activity on the dopamine system including the transporter. We designed two Positron Emission Tomography studies (a) to investigate cocaine's activity on dopamine release in humans and (b) on regional cerebral blood flow. In study one, 11 male subjects were injected within [1 IC]-Raclopride, a positronemitting dopamine D2 antagonist. 0 to 10 minutes after the raclopride injection subjects were injected with either saline (baseline scan) or with 48mg of cocaine hydrochloride (drug scan). Time - Activity curves (TAC) were obtained for both conditions in putamen and cerebellum. In study two, three subjects were injected with 015 water 30 to 180 seconds after cocaine injection. All subjects reported subjective euphoriant effects on Visual Analog Scales. The area under the TAC (corrected for the amount of injected dose of radioactivity) was 251.0 1 39.1 in the cocaine condition (t=6.7, p<0.0001, df=10). In study two, global cerebral blood flow was reduced 27 1 9% using in three subjects. Maximal decreases were seen 60 seconds after cocaine injection. We demonstrated that doses of cocaine similar to typical "street doses" demonstrated significant displacement of a radiolabelled dopamine D2 receptor antagonist. This finding seems consistent with the dopamine hypothesis of cocaine's actions and is of potential relevance in the search for pharmacological treatments of cocaine abuse. Furthermore we replicated the finding of other studies, that cocaine reduces global blood flow acutely. Future Plans: Analyses of regional patterns of CBF changes as well as correlations with behavioral measures are under way, and we will continue to study subjects with 015 to better define the "time window" of cocaine effects and to plot dose response relationships within individuals.